Widespread transcription at neuronal activity-regulated enhancers

Tae Kyung Kim, Martin Hemberg, Jesse M. Gray, Allen M. Costa, Daniel M. Bear, Jing Wu, David A. Harmin, Mike Laptewicz, Kellie Barbara-Haley, Scott Kuersten, Eirene Markenscoff-Papadimitriou, Dietmar Kuhl, Haruhiko Bito, Paul F. Worley, Gabriel Kreiman, Michael E. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified ∼12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

Original languageEnglish (US)
Pages (from-to)182-187
Number of pages6
JournalNature
Volume465
Issue number7295
DOIs
StatePublished - May 13 2010

ASJC Scopus subject areas

  • General

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